Journal article
Menaquinone Analogs Inhibit Growth of Bacterial Pathogens
Antimicrobial agents and chemotherapy, Vol.57(11), pp.5432-5437
11/2013
DOI: 10.1128/AAC.01279-13
PMCID: PMC3811306
PMID: 23959313
Abstract
Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of
Staphylococcus aureus
,
Bacillus anthracis
,
Streptococcus pyogenes
, and
Streptococcus agalactiae
at concentrations of 10 to 200 μg/ml. Coenzyme Q1 reduced the ability of
S. aureus
to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit
S. aureus
growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents.
Details
- Title: Subtitle
- Menaquinone Analogs Inhibit Growth of Bacterial Pathogens
- Creators
- Patrick M Schlievert - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, USAJoseph A Merriman - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAWilmara Salgado-Pabón - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAElizabeth A Mueller - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAAdam R Spaulding - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USABao G Vu - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAOlivia N Chuang-Smith - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, USAPetra L Kohler - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, USAJohn R Kirby - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.57(11), pp.5432-5437
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- DOI
- 10.1128/AAC.01279-13
- PMID
- 23959313
- PMCID
- PMC3811306
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Language
- English
- Date published
- 11/2013
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984002399202771
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